miR-483-3p plays an oncogenic role in esophageal squamous cell carcinoma by targeting tumor suppressor EI24

Abstract

microRNAs (miRNAs), through negatively regulating their target genes, influence the development and progression of many cancers. Previously, we found miR-483 was overexpressed in esophageal squamous cell carcinoma (ESCC) tissues, and its overexpression was negatively correlated with the prognosis and positively correlated with multidrug resistance of ESCC, but whether it could affect the biological role of proliferation and migration in ESCC cell lines is unknown. In the present study, we found miR-483-3p was overexpressed in ESCC cell lines as compared with the normal esophageal squamous epithelial cell line. Functional experiments in vitro showed that miR-483-3p could promote the proliferation, migration, transformation of cell cycle from G1 phase to G2 phase of ESCC cells and could inhibit cells' sensitivity to chemotherapy drugs. Nude mouse tumorigenicity assay indicated that miR-483-3p could promote the growth of ESCC cells in vivo. Western blot assay showed that ectopic expression of miR-483-3p in ESCC cells could downregulate the protein level of etoposide induced 2.4 (EI24), which is a tumor suppressor and has not been reported in ESCC. Luciferase reporter assay demonstrated that EI24 was a direct target of miR-483-3p. Collectively, our study demonstrated that miR-483-3p could promote ESCC progression at least in part through directly targeting EI24, supplying a potential strategy for miRNA-based ESCC therapy.

Keywords: EI24; drug resistance; esophageal squamous cell carcinoma; miR-483-3p; migration; proliferation.